Universität zu Köln

Albin, Jan, Fahrig, Luca, Siemanowski, Janna, Rehkaemper, Jan, Gebauer, Florian, Zander, Thomas, Buettner, Reinhard, Bruns, Christiane Josephine, Schroeder, Wolfgang, Alakus, Hakan, Hieggelke, Lena and Quaas, Alexander . FGFR2-amplified tumor clones are markedly heterogeneously distributed in carcinomas of the upper gastrointestinal tract. J. Cancer Res. Clin. Oncol.. NEW YORK: SPRINGER. ISSN 1432-1335

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Abstract

Background FGFR2 is a therapy-relevant target in tumors of the upper gastrointestinal tract (GIT), and clinical trials are currently underway to test the efficacy of FGFR2 inhibitors. Tumor heterogeneity is one of the relevant causes of treatment failure. Almost nothing is known about the heterogeneous distribution of FGFR2-amplified clones in adenocarcinomas of the upper GIT. Patients and methods To assess FGFR2 gene copy number alteration and intratumoral heterogeneity of upper GIT adenocarcinomas, we analyzed 893 patient-derived formalin-fixed paraffin-embedded tumor specimens, including primary operated and neoadjuvant-treated tumors (462 gastric carcinomas and 429 esophageal adenocarcinomas) as well as complementary lymph node and distant metastasis by fluorescence in situ hybridization. Results Twenty-six gastric tumors (5.6%) and 21 esophageal adenocarcinomas (4.9%) showed FGFR2 amplification. Overall, 93% of gastric carcinomas and 83% of esophageal carcinomas showed heterogeneous amplification. FGFR2 amplification was found in different histological growth patterns, including intestinal and diffuse type according to the Lauren classification. In the primary gastric carcinoma group, FGFR2 amplification was associated with poor prognosis (p = 0.005). Conclusion Homogeneous FGFR2 amplification in tumors of the upper GIT is the exception. This has highly relevant implications in the nature of FGFR2 diagnostics (sufficient tumor cell number, determination of amplification at metastasis versus primary tumor, etc.) and on the response probability of appropriate inhibitors. It is relevant that the often poorly treatable and aggressive subtype of diffuse carcinomas (poorly cohesive carcinomas) also shows FGFR2 amplification and that an individualized therapy option with FGFR2 inhibitors could be an option in this group.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Albin, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Fahrig, Luca UNSPECIFIED UNSPECIFIED UNSPECIFIED Siemanowski, Janna UNSPECIFIED UNSPECIFIED UNSPECIFIED Rehkaemper, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Gebauer, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Zander, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruns, Christiane Josephine UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeder, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Alakus, Hakan UNSPECIFIED UNSPECIFIED UNSPECIFIED Hieggelke, Lena UNSPECIFIED UNSPECIFIED UNSPECIFIED Quaas, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-661605
DOI:	10.1007/s00432-022-04460-w
Journal or Publication Title:	J. Cancer Res. Clin. Oncol.
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-1335
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GASTRIC-CANCER; INTRATUMORAL HETEROGENEITY; GENE AMPLIFICATION; FGFR2 GENE; HER2; EXPRESSION; GROWTH; ADENOCARCINOMA; CHEMOTHERAPY; SURVIVAL Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/66160